CN111171252A - 类硫酸软骨素聚合物水凝胶及其制备方法 - Google Patents
类硫酸软骨素聚合物水凝胶及其制备方法 Download PDFInfo
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Abstract
本发明提供一种类硫酸软骨素聚合物水凝胶及其制备方法，由以下物质制备所得：可聚合单糖单体和可聚合磺酸单体、交联剂。本发明从化学仿生合成的角度出发，通过交联反应成功制备了一系列不同糖和磺酸基团含量的类硫酸软骨素聚合物水凝胶，模拟了细胞外基质中磺化的糖胺聚糖结构和功能，对骨髓间充质干细胞的增殖和分化具有重要影响。
Description
技术领域
本发明属于生物医用材料领域，具体涉及一种类硫酸软骨素聚合物水凝胶及其制备方法。
背景技术
硫酸软骨素作为糖胺聚糖(GAGs)的典型代表，有着磺化多糖结构，广泛存在于软骨组织的细胞外基质(ECM)中，对软骨细胞和骨髓间充质干细胞(BMSCs)生理行为的调节具有显著的生物活性。此外，值得注意的是，硫酸软骨素也存在于一定量的骨组织结构中，参与骨代谢过程。因此，硫酸软骨素基生物材料以其独特的生物活性和功能，在组织工程、疾病治疗等领域得到了广泛的应用。然而，硫酸软骨素的一些固有缺陷给它们的应用带来了不可忽视的限制，例如纯度不高，多糖骨架结构复杂和磺化度不可控制。此外，与其他GAGs一样，对硫酸软骨素的一些物理或化学修饰(如加热和辐照)将导致其生物活性降低，进一步限制其生物应用。
发明内容
针对上述技术问题，本发明提供一种类硫酸软骨素聚合物水凝胶及其制备方法。
具体技术方案为：
类硫酸软骨素聚合物水凝胶，由以下物质制备所得：可聚合单糖单体和可聚合磺酸单体、交联剂。
所述的可聚合单糖单体，为乙烯类，丙烯酰胺类，丙烯酸酯类单糖中的一种。
所述的可聚合单糖单体，为阿拉伯糖、来苏糖、葡萄糖、甘露糖、果糖、半乳糖中的一种。
所述的可聚合磺酸单体为乙烯类，丙烯酰胺类，丙烯酸酯类单体中的一种，还可以为乙烯类，丙烯酰胺类，丙烯酸酯类单体对应的钠盐和钾盐中的一种。
所述的交联剂为不同分子量的聚乙二醇二丙烯酸酯PEGDA，或者N,N'-亚甲基双丙烯酰胺。
上述类硫酸软骨素聚合物水凝胶的制备方法，所述的可聚合单糖单体和可聚合磺酸单体、交联剂在剧烈搅拌下完全溶解于PBS中；然后将光引发剂I2959加入到混合溶液中，在365nm紫外光下引发聚合，得到不同糖和磺酸单元含量的类硫酸软骨素聚合物水凝胶。
溶解于PBS时保持pH7.4。
所述的光引发剂I2959的用量为占单体总量的0.5mol％。
还提供另外一种制备方法，所述的类硫酸软骨素聚合物水凝胶的制备方法，所述的可聚合单糖单体和可聚合磺酸单体、交联剂在剧烈搅拌下完全溶解于PBS中；加入引发剂过硫酸铵或过硫酸钾，在60℃下引发聚合。
还提供另外一种制备方法，所述的类硫酸软骨素聚合物水凝胶的制备方法，所述的可聚合单糖单体和可聚合磺酸单体、交联剂在剧烈搅拌下完全溶解于PBS中；加入过硫酸铵和四甲基乙二胺，用氧化还原体系引发聚合。
本发明所得的类硫酸软骨素聚合物水凝胶，获得的不同糖和磺酸单元含量的类硫酸软骨素聚合物水凝胶，命名为Gel-MAG、Gel-AMPS和Gel-MxSy，x和y代表2-甲基丙烯酰胺吡喃葡萄糖(MAG/M)和2-丙烯酰氨基-2-甲基-1-丙烷磺酸(AMPS/S)的投料比。
本发明提供的类硫酸软骨素聚合物水凝胶及其制备方法，具有的有益效果：
本发明从化学仿生合成的角度出发，通过自由基聚合反应成功制备了一系列不同糖和磺酸基团含量的类硫酸软骨素聚合物水凝胶，模拟了细胞外基质中磺化的糖胺聚糖结构和功能，对骨髓间充质干细胞的增殖和分化具有重要影响。
附图说明
图1是实施例1中类硫酸软骨素聚合物水凝胶制备示意图；
图2是实施例1中类硫酸软骨素聚合物水凝胶细胞增殖实验测试结果；
图3是实施例1中类硫酸软骨素聚合物水凝胶在基础培养基中调控骨髓间充质干细胞成软骨分化的实验测试结果；
图4是实施例1中类硫酸软骨素聚合物水凝胶在成软骨诱导培养基中调控骨髓间充质干细胞成软骨分化的实验测试结果；
图5是实施例1中类硫酸软骨素聚合物水凝胶在成骨诱导培养基中调控骨髓间充质干细胞成骨分化的实验测试结果。
具体实施方式
实施例1
类硫酸软骨素聚合物水凝胶的制备方法，包括以下步骤：
乙烯基单糖、磺酸单体和聚乙二醇二丙烯酸酯PEGDA(Mn＝600,20mol％)在剧烈搅拌下完全溶解于PBS(pH7.4)中。
其中，单糖单体为2-甲基丙烯酰胺吡喃葡萄糖(MAG/M)，磺酸单体为2-丙烯酰氨基-2-甲基-1-丙烷磺酸(AMPS/S)，单体总浓度为1mol/L。
通过改变MAG和AMPS的初始投料比，设计和调整所得类硫酸软骨素聚合物水凝胶中的糖和磺酸单元的比例。
然后将光引发剂I2959加入到混合溶液中，在紫外光下引发聚合，得到不同糖和磺酸单元含量的类硫酸软骨素聚合物水凝胶。
将光引发剂I2959用量为占双键单体总量的0.5mol％。
得到不同糖和磺酸单元含量的类硫酸软骨素聚合物水凝胶，命名为Gel-MAG、Gel-AMPS和Gel-MxSy，其中x和y代表MAG和AMPS的投料比。
Gel-MAG和Gel-AMPS是由MAG和AMPS与一定量的PEGDA共同制备的水凝胶。
Gel-PEGDA是由PEGDA加一定量引发剂I2959制备的水凝胶。
图1是实施例1中类硫酸软骨素聚合物水凝胶制备示意图；
图2是实施例1中类硫酸软骨素聚合物水凝胶细胞增殖实验测试结果；
图3是实施例1中类硫酸软骨素聚合物水凝胶在基础培养基中调控骨髓间充质干细胞成软骨分化的实验测试结果；
图4是实施例1中类硫酸软骨素聚合物水凝胶在成软骨诱导培养基中调控骨髓间充质干细胞成软骨分化的实验测试结果；
图5是实施例1中类硫酸软骨素聚合物水凝胶在成骨诱导培养基中调控骨髓间充质干细胞成骨分化的实验测试结果。
表1是实施例1中类硫酸软骨素聚合物水凝胶元素分析测试结果。
表1
实施例2
乙烯基单糖、磺酸单体和N,N'-亚甲基双丙烯酰胺(10mol％)在剧烈搅拌下完全溶解于PBS(pH7.4)中。
其中，单糖单体为2-甲基丙烯酰胺吡喃葡萄糖(MAG/M)，磺酸单体为对苯乙烯磺酸钠(SS/S)，单体总浓度为1.5mol/L。
通过改变MAG和SS的初始投料比，设计和调整所得类硫酸软骨素聚合物水凝胶中的糖和磺酸单元的比例。
然后将引发剂过硫酸铵加入到混合溶液中，在60℃下引发聚合，得到不同糖和磺酸单元含量的类硫酸软骨素聚合物水凝胶。
将引发剂过硫酸铵用量为占双键单体总量的0.5mol％。
得到不同糖和磺酸单元含量的类硫酸软骨素聚合物水凝胶，命名为Gel-MAG、Gel-SS和Gel-MxSy，其中x和y代表MAG和SS的投料比。
Gel-MAG和Gel-SS是由MAG和SS与一定量的N,N'-亚甲基双丙烯酰胺共同制备的水凝胶。
实施例3
乙烯基单糖、磺酸单体和聚乙二醇二丙烯酸酯PEGDA(Mn＝200,20mol％)在剧烈搅拌下完全溶解于PBS(pH7.4)中。
其中，单糖单体为2-甲基丙烯酰胺吡喃葡萄糖(MAG/M)，磺酸单体为甲基丙烯磺酸钠(MS/S)，单体总浓度为2mol/L。
通过改变MAG和SS的初始投料比，设计和调整所得类硫酸软骨素聚合物水凝胶中的糖和磺酸单元的比例。
然后将引发剂过硫酸铵和四甲基乙二胺加入到混合溶液中，在40℃下引发聚合，得到不同糖和磺酸单元含量的类硫酸软骨素聚合物水凝胶。
将引发剂过硫酸铵和四甲基乙二胺用量为各占双键单体总量的0.5mol％。
得到不同糖和磺酸单元含量的类硫酸软骨素聚合物水凝胶，命名为Gel-MAG、Gel-MS和Gel-MxSy，其中x和y代表MAG和MS的投料比。
Gel-MAG和Gel-MS是由MAG和MS与一定量的PEGDA(Mn＝200)共同制备的水凝胶。
Claims (10)
1.类硫酸软骨素聚合物水凝胶，其特征在于，由以下物质制备所得：可聚合单糖单体和可聚合磺酸单体、交联剂。
2.根据权利要求1所述的类硫酸软骨素聚合物水凝胶，其特征在于，所述的可聚合单糖单体，为乙烯类，丙烯酰胺类，丙烯酸酯类单糖中的一种。
3.根据权利要求1所述的类硫酸软骨素聚合物水凝胶，其特征在于，所述的可聚合单糖单体，为阿拉伯糖、来苏糖、葡萄糖、甘露糖、果糖、半乳糖中的一种。
4.根据权利要求1所述的类硫酸软骨素聚合物水凝胶，其特征在于，所述的可聚合磺酸单体为乙烯类，丙烯酰胺类，丙烯酸酯类单体中的一种，还可以为乙烯类，丙烯酰胺类，丙烯酸酯类单体对应的钠盐和钾盐中的一种。
5.根据权利要求1所述的类硫酸软骨素聚合物水凝胶，其特征在于，所述的交联剂为不同分子量的聚乙二醇二丙烯酸酯PEGDA，或者N,N'-亚甲基双丙烯酰胺。
6.根据权利要求1到5所述的类硫酸软骨素聚合物水凝胶的制备方法，其特征在于，所述的可聚合单糖单体和可聚合磺酸单体、交联剂在剧烈搅拌下完全溶解于PBS中；然后将引发剂加入到混合溶液中，在365nm紫外光下或一定温度下引发聚合，得到不同糖和磺酸单元含量的类硫酸软骨素聚合物水凝胶。
7.根据权利要求6所述的类硫酸软骨素聚合物水凝胶的制备方法，其特征在于，溶解于PBS时保持pH7.4。
8.根据权利要求6所述的类硫酸软骨素聚合物水凝胶的制备方法，其特征在于，所述的引发剂的用量为占单体总量的0.5mol％。
9.根据权利要求1到5所述的类硫酸软骨素聚合物水凝胶的制备方法，其特征在于，所述的可聚合单糖单体和可聚合磺酸单体、交联剂在剧烈搅拌下完全溶解于PBS中；加入引发剂过硫酸铵或过硫酸钾，在60℃下引发聚合。
10.根据权利要求1到5所述的类硫酸软骨素聚合物水凝胶的制备方法，其特征在于，所述的可聚合单糖单体和可聚合磺酸单体、交联剂在剧烈搅拌下完全溶解于PBS中；加入过硫酸铵和四甲基乙二胺，用氧化还原体系引发聚合。
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